Abstract
BackgroundAlteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy.MethodologyWe conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients’ microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy.ResultsPrior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health.ConclusionOur findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.
Highlights
The human gut is colonized by a large number of commensal microorganisms which play important roles in maintenance of good health
Prior to commencement of chemotherapy, gut microbiota in children with acute lymphoblastic leukemia (ALL) had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus
The microbiota composition remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health
Summary
The human gut is colonized by a large number of commensal microorganisms which play important roles in maintenance of good health. In a recent cross-sectional study of young adult survivors of childhood ALL (median age = 26 years old) with a median period of 18.5 years off-chemotherapy, we reported reduced gut microbiota diversity and distinct gut microbiota profile as compared to controls who had no history of cancer These survivors exhibited increased markers of immune activation [12] and higher prevalence of metabolic syndrome [13]. It is unclear if the microbiota diversity observed in these young adult survivors of ALL is a consequence of chemotherapy exposure during their childhood and has persisted over time Understanding this is important in the context of late effects in childhood cancer survivors, which include gastrointestinal complications, chronic inflammation, metabolic syndrome, and cardiovascular disease [9, 10, 13, 14]; conditions, which have all been, associated with gut dysbiosis in the general population [6, 15, 16]. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy
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